Paraquat, silica, and asbestos are important causes of environmental lung disease because of their widespread use and because of the large numbers of people exposed. All three agents are capable of directly injuring lung parenchyma, but they also have been shown to induce a neutrophil alveolitis in the early stage of low dose, chronic exposure. This neutrophil alveolitis precedes the classic findings of interstitial fibrosis seen after long term exposure to silica and asbestos or after acute ingestion, inhalation, or dermal exposure to paraquat. We propose to study the mechanisms of lung injury by these agents with special emphasis towards their roles in the recruitment and activation of inflammatory cells to damage lung parenchyma even at extremely low doses. The research model will be the rat lung explant system. This model allows separation of lung tissue from host inflammatory cells while retaining the basis architectural unit of the lung -the alveolus. It has been used extensively in evaluation of high dose, acute paraquat exposure which will provide background for our studies. In our laboratory we have used the rat lung explant system to study bleomycin, a chemotherapeutic agent with a similar mechanism of direct injury as paraquat. We have found that even low dose exposure to bleomycin results in the release of factors chemotactic for neutrophils, and that neutrophils greatly enhance lung tissue injury even at very low doses of bleomycin. In view of the results from the bleomycin studies, the proposed studies with paraquat are important first to establish a dose response relationship of paraquat induced lung injury since inflammatory cell recruitment may cause injury at previously acceptable exposure levels. Second, the comparison of paraquat, silica and asbestos initiated, inflammatory cell mediated lung injury may reveal a common mechanism of injury by these agents at low dose, chronic exposure.